Efficacy of radiotherapy in stabilization of oligoprogressive lesions of malignant melanoma treated with immunotherapy.

Abstract

Background: This study aims to evaluate the effectiveness of radiotherapy (RT) in stabilizing oligoprogressive disease (OPD) in melanoma patients undergoing immunotherapy. We hypothesize that RT's efficacy in disease stabilization is influenced by factors such as dose, fractionation, metastatic burden, and the timing of OPD onset relative to immunotherapy initiation.

Materials and methods: A retrospective observational study was conducted at two Czech university hospitals. Inclusion criteria encompassed metastatic melanoma patients undergoing immunotherapy with checkpoint inhibitors who developed OPD between January 2018 and May 2023. Exclusion criteria included central nervous system (CNS) involvement, discontinuation of systemic therapy during or after RT, and treatments other than immune checkpoint inhibitors. Patients were stratified based on RT initiation timing (< 6 months or > 6 months from immunotherapy start) to assess primary and acquired resistance. 34 patients were included, with RT administered for extracranial OPD. Among these, local control was achieved in 21 patients.

Results: Higher doses of RT [> 40 Gy the equivalent dose in 2 Gy fractions (EQD2)] correlated with improved local control. Patients with fewer than five irradiated lesions experienced better progression-free survival (PFS) and overall survival (OS), however, the difference did not reach statistical significance. Multivariate analysis revealed that patients who received RT after > 6 months since initiation of immune checkpoint inhibitor (ICI) had significantly longer PFS. This study suggests, that RT is a viable option for stabilizing OPD in melanoma patients treated with immunotherapy, especially when administered later in the treatment course.

Conclusions: Improved OS and PFS outcomes suggest that delayed OPD may indicate acquired resistance, which benefits from RT. Future studies should refine RT parameters and patient selection criteria to optimize clinical outcomes.